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Biomaterials Approaches for Utilizing the Regenerative Potential of the Peripheral Nerve Injury Microenvironment

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Biomaterials Approaches for Utilizing the Regenerative Potential of the Peripheral Nerve Injury Microenvironment Wayne State University Wayne State University Dissertations 1-1-2017 Biomaterials Approaches For Utilizing The Regenerative Potential Of The eP ripheral Nerve Injury Microenvironment Melissa Renee Wrobel Wayne State University, Follow this and additional works at: https://digitalcommons.wayne.edu/oa_dissertations Part of the Biomedical Engineering and Bioengineering Commons, Cell Biology Commons, and the Materials Science and Engineering Commons Recommended Citation Wrobel, Melissa Renee, "Biomaterials Approaches For Utilizing The Regenerative Potential Of The eP ripheral Nerve Injury Microenvironment" (2017). Wayne State University Dissertations. 1899. https://digitalcommons.wayne.edu/oa_dissertations/1899 This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. BIOMATERIALS APPROACHES FOR UTILIZING THE REGENERATIVE POTENTIAL OF THE PERIPHERAL NERVE INJURY MICROENVIRONMENT by MELISSA RENEE WROBEL DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2017 MAJOR: BIOMEDICAL ENGINEERING Approved By: Advisor Date © COPYRIGHT BY MELISSA RENEE WROBEL 2017 All Rights Reserved DEDICATION In Loving Memory of Regina Stella Wrobel 1936-2017 ii ACKNOWLEDGEMENTS A part of me always wanted to earn a PhD, but I lacked the self-confidence to make that goal a reality. So first and foremost, I have to thank Harini Sundararaghavan (aka “Dr.S”) for inviting me into her lab and affording me this opportunity. Without that invitation, this dissertation would not exist. Thank you Dr.S for encouraging me to pursue opportunities I would have other- wise passed up, for challenging me to step outside of my comfort zones (all those presentations!), and for reassuring me during times of disappointment. I am finishing this degree a more inde- pendent and more confident person than when I started and I owe that all to you. Next, I need to thank my other committee members, Karen Beningo, Howard Matthew, and Weiping Ren for their guidance and perspective. I deeply admire you all and look forward to both professional and friendly relationships in the future. I also want to thank Wayne State Uni- versity, the College of Engineering, and the Biomedical Engineering department for supporting me academically and financially. I have been beyond fortunate for the support provided to me by this institution, its faculty and its students. There truly is a sense of community here that I have never felt more strongly than I do now and that I will never forget. I felt no greater sense of community than with my peers and colleagues in Dr.S’s lab, especially Tonya Whitehead, Beth Steel, and Lizzy Mays. As my time as a PhD candidate at Wayne State draws near, I have fallen victim to “senior-itis”, sometimes feeling desperate to move on and move out. Lizzy, seeing you finishing up your coursework and finally getting into your research, reminds me of how exciting science can be during those first experiments and why I wanted to do this in the first place. You’ve also taught me that I am the kind of person capable of making a fast friend. I’m sorry to be leaving after only a couple years with you. I really look forward to returning for your own dissertation defense! Beth, you have taught me the importance of opening up to other people and the value of sharing my experiences. I could have gone through my entire college career doing everything on iii my own and taking help from no one, but what a hollow education I would have received. “Bounc- ing” ideas off one another has produced some of our best, and potentially some of our worst too. Either way, I’m grateful to have had those times. You are passionate about life and science and I so admire your tenacity. Tonya, you have “forced” me into a lot of different activities during my time at Wayne State. And I cannot thank you enough. You pressured me to participate in groups (including TBP, BMES, SWE, Journal clubs, teaching, etc) that resulted in leadership opportunities, professional experi- ence, and lifelong friends. I’m not sure how I will ever repay you for helping me have such a rich experience here. Thank you for deciding to be my friend after all ;-) and for letting me by myself, but now a slightly better version thanks to you. Tonya, Beth, and Lizzy, I can imagine no three better women to have gone through this PhD journey with than you. I feel so ridiculously lucky to have spent every day not just with lab mates but with true friends. Special thanks to the undergrads that have gone through the Sundara- raghavan lab through the years. There are too many of you to name specifically but you know who you are and I thank you. Dr.S’s lab is truly the best group of people at Wayne State and if anyone wants to challenge us…bring it on! I also need to thank my oldest and closest friends, my brother Matthew Wrobel and my “sister” Jennifer (Thomas) Miller. Jen, thank you for letting me type so obnoxiously loud on my keyboard during undergrad that it kept you awake at night. I needed those grades to get me where I am now. With you two I get to turn off the science for a few hours and just be silly. You two remind me to never take myself too seriously and to always have fun. So, as soon as I’m done with this degree, do you guys wanna play Mario Party? I also need to thank my incredible boyfriend Mat Lutz. Having endured my senior year at Michigan and all 7 years of graduate school at Wayne State, you’ve truly tolerated all the ups and downs of this degree, and have somehow remained so unbelievably dependable. You’ve provided me with everything from comfort and calm to candy and caffeine (you literally delivered to me iv whatever I asked for during grueling hours of writing and at all hours of the day!) You’ve kept me sane and probably alive (so klutzy!). As the street smarts to my books smarts, you are my indis- pensable other half. I am so grateful for you. Also, I begrudgingly thank you for making me get our two cats, Max and Kirby. I never knew I could love two fur balls so much. Thankfully, they are good listeners. Every person mentioned here should probably thank the cats because it means you had to listen to me complain at least one fewer time! Finally, I need to thank my entire family. Thank you to every aunt, uncle, and cousin (there are too many of you to name!) Special thanks to my grandparents, Robert and Rosemarie Francis and Robert and Regina Wrobel. Thank you for your appearances at my school events throughout the years. Thank you for your unwavering support. I know that you are all my biggest fans. It may not have seemed like it, but I’m grateful to each one of you who has ever asked me “when will you graduate?” Your consistent reminders only showed how much you care. Most importantly, thank you to my parents, Ken and Renee (“Lady”) Wrobel. You are the two most loving and gen- erous parents, possibly in existence. Everything I have, everything I am, and everything I will ever be, I owe to you two. I love you Mom and Dad and I hope I’ve made you proud. Earning this degree has been more than I could have ever imagined. To anyone who had a part in my life the past several years, no matter how small, I thank you. v TABLE OF CONTENTS DEDICATION............................................................................................................................. ii ACKNOWLEDGEMENTS ..........................................................................................................iii LIST OF TABLES ......................................................................................................................ix LIST OF FIGURES .................................................................................................................... x CHAPTER 1: INTRODUCTION AND BACKGROUND .............................................................. 1 Prevalence and Significance of Peripheral Nerve Injuries ....................................................... 1 Characterization of the Peripheral Nerve Injury Microenvironment ......................................... 3 Problem Statement: Current Treatments are Insufficient to Repair Large Nerve Gaps ..........11 Literature Review and Motivating Work .................................................................................15 Summary ...............................................................................................................................22 CHAPTER 2: POSITIVE AND NEGATIVE CUES FOR MODULATING NEURITE DYNAMICS AND RECEPTOR EXPRESSION.......................................................................................................... 26 Introduction ...........................................................................................................................26 Experimental .........................................................................................................................28 Materials ............................................................................................................................28 Isolation and Characterization of Spinal Cord Matrix Proteins ............................................28 Cell Culture ........................................................................................................................29 Microscopy and Image Analysis .........................................................................................30
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